Bishydantoic acid amides from alpha, omega-diamines



United? StatesPatefifTQ C6 2,928,874.

1 2 2,928,8 7 1 apparent from this disclosure to those skilled in the art.

BISHYDANTOIC ACID EXAMPLE 1 IAMINES As typical of the bis-hydantoamides obtained from reac- Seymour L. Shapiro, Hastings on Hudson, and Louis U011 f p lf y 811111165 0 the YP ;X-NH

Freedman, Bronxviile, N.Y., assignors to U.S. Vitamin the following experlmental procedure 1s glven.

n L PatentedlMar. 15,1960

many modificatiosn in materials and methods will be and Pharmaceutical Corporation, New York, N.Y., a A solution of 6.5 g. of ethyl hydantoate in 50 ml. of corporation of Delaware methanol was-treated with 3.0 g; (0.037 equivalent) of 72% aqueous 1,6-hexanediamine. After storage at 20 No g g lgg rggg 'ggg 1959 m C. for several days, the product (4.77 g.), M.P.

210-220 C. was separated in 81% yield and upon 6 Cl msrecrystallization (ethanol-water) the formed N,N'-hexamethylene-bis-hydantoamide melted at 221-222 C.

This invention is concerned with N,N'-polymethylene- Analysis.-Calcd. for C H N O C, 45.6; H, 7.7; bis-hydrantoamides of the following formula N, 26.6. Found: C, 45.8; H, 7.7; N, 26.6.

In a similar manner and using variants of l l 2( 2)1t 2 NH -O-NH-CH:CNXN-C-OHz-NHCNH:

l l l l the corresponding bis-hydantoamides characterized in Table I were prepared.

Table I BIS-HYDANTOAMIDEB i t i i i i i i NH,-oN-0 HrC-N( Om) .N0-0H,-N-0-NH| Analyses, percent M.P., n 0. Formula Carbon Hydrogen Nitrogen Calcd. Found Galcd. Found Galcd. Found GsHmNt04. 36.9 36.8 6.2 6.1 32.3 32.4 0.3mm..-" 39.4 39.3 6.6 6.4 CroHrnNaOt--. 41.7 41.8 7.0 7.1 29.2 28.6 CnHnNgOL 43. 7 43. 4 7. 3 6. 7 27. 8 27. 9 CxsHzoNs04- 47. 3 47. 2 7. 9 7. 8 25. 4 25. 3

where X is a polymethylene chain of the type EVAMPLE 2 --(CH A solution of 6.85 g. of ethyl hydantoate in 50 ml. wherein n is a small whole number ranging from of hot methanol was cooled and treated with 2.70 g. of and an xylylene group of the type m-xylene diamine. After storage at 20 C. for 72 hours,

the product, 2.9 g. (44%), was separated and recrystallized (ethanol-water) and melted at 220-222 C.

Analysis.-Calcd. for C H N O C, 50.0; H, 6.0; N, 25.0. Found: C, 49.8; H, 6.0; N, 25.0.

The product so formed is the N,N-(m-xylylene)-bis The compounds of this invention are Stable, high hydantoamide and has the following structure:

melting, white, somewhat water-soluble, crystalline solids which are conveniently prepared by reaction of the 1? 1? H I diamine NH -X-NH with ethyl hydantoate in a lower NHPC-N CHPo-N-CH alcohol.

The compounds of this invention show a variety of valuable pharmacological properties, particularly in their effect on the central nervous system, wherein anticon- In a similar manner using oxylylene diamine, and vulsant eifects, depression of the central nervous system, p-xylylene diamine, the corresponding N,N'-oand and potentiation of Metrazole convulsions are noted p-xylylene-bis-hydantoamides may be prepared. efiects with individual species. The novel compounds of this invention can be com- This invention will be more fully described from the bined with solid or liquid pharmaceutical carriers and examples which follow. These examples are set forth formulated in the form of tablets, powder packets or by way of illustration only, and it will be understood capsules, or dissolved in suitable solvents for oral and that the invention is not to be construed as limited in parenteral administration for human or veterinary use. spirit or in scope by the details contained therein, since it is to be understood that it is intended to cover all 3 V changes and modifications of the examples herein chosen 2. The compound of claim 1, wherein X is for the purpose of illustration which do not constitute departures from the spirit and scope of the invention 2)n""' We claim: and n is 4. l. The compound 5 3. Thecompound of claim 1, wherein X is 1 i i i i nmare-N4:Hi-%N-xN%-0H,N- -NH, and n is 5 0 o 4. The compound of claim 1, wherein X is wherein X is selected from the group consisting of 10 s 2) 2)n' and n is 6. and 5. The compound of claim 1, wherein X is 15 z) and n is 1.

6. The compound of claim 1, wherein X is m-xylylenc.

where n 18 an integer selected from the group cons sting N 0 references cited 

1. THE COMPOUND 